Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Octreotide acetate is a long-acting analogue of the naturally occurring inhibitory gastrointestinal peptide, somatostatin. We tested the efficacy of octreotide in controlling the symptoms of dumping syndrome in response to a provocative meal in a randomized, double-blinded, crossover trial in nine severely affected patients. Pretreatment with octreotide acetate (100 micrograms injected subcutaneously) reduced postprandial dumping symptoms from a mean +/- SEM score of 15.7 +/- 1.6 (placebo treatment day) to 4.6 +/- 1.7. With placebo treatment, all nine patients became symptomatic in response to the meal, whereas with octreotide treatment, symptoms occurred in only two of nine patients. Similarly, all placebo-treated patients showed a postprandial increase in pulse rate to a mean +/- SEM of 105 +/- 6 beats per minute, whereas only one of nine octreotide-treated patients showed an increase in pulse rate (mean +/- SEM, 80 +/- 3 beats per minute). These differences were also statistically significant. While no significant changes were observed in postprandial hematocrit values or osmolality between placebo and octreotide treatments, octreotide prevented hypoglycemia in four affected patients and significantly inhibited insulin release. We conclude that octreotide is a useful tool in the treatment of patients with severe, refractory dumping syndrome.
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PMID:Control of dumping symptoms by somatostatin analogue in patients after gastric surgery. 192 23

The mouse corticotrope tumor cell line AtT-20/D16v was used to investigate the effects of chronic treatment with various secretagogues on individual components of the secretory pathway. Secretagogues acting in part through receptors linked to guanine nucleotide-binding regulatory proteins [CRF and somatostatin (SS)] and agents by-passing membrane receptors (phorbol myristate acetate and dexamethasone) were examined. Effects on the secretory product were evaluated by measuring levels of pro-ACTH/endorphin mRNA and hormone secretion. Effects on posttranslational processing enzymes were evaluated by measuring levels of the mRNAs encoding carboxypeptidase-E and peptidyl-glycine-alpha-amidating monooxygenase (PAM); cellular levels of PAM activity were also measured. The mRNAs encoding the G-proteins in AtT-20 cells were identified, and secretagogue effects on the G-protein signal transduction system were evaluated by measuring levels of the mRNAs encoding (alpha s, alpha)i2, and beta 2. No single parameter adequately characterizes the regulatory state of the complex secretory apparatus. Although levels of pro-ACTH/endorphin (PAE) mRNA accurately reflected hormone secretion after chronic CRF or dexamethasone treatment, chronic SS treatment elevated PAE mRNA levels in the face of reduced hormone secretion. Levels of PAM mRNA generally changed in parallel with levels of PAE mRNA; in contrast, levels of carboxypeptidase-E mRNA were unaffected by any of the secretagogues tested. Secretagogues acting through distinct G-proteins (CRF and SS) as well as dexamethasone brought about a coordinate increase in the level of the mRNAs encoding the three G-protein subunits examined. Treatment with phorbol myristate acetate caused a slight decrease in the levels of the G-protein subunit mRNAs.
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PMID:Effect of secretagogues on components of the secretory system in AtT-20 cells. 196 78

Mammalian prosomatostatin (pro-S) undergoes extensive processing at the C-terminal segment where the somatostatin-like biological activities (S-14 and S-28) reside. The recent discovery of pro-S-(1-10) (antrin) as a prominent mature product in the stomach suggests that pro-S may also be processed at the N-terminus. In the present study we have developed an antibody directed against the N-terminal segment of pro-S-(1-10) capable of detecting peptides extended at the C-terminus of pro-S-(1-10) to characterize N-terminal processing of rat pro-S. Specifically, we have 1) examined the relative abundance of pro-S-(1-10)-like immunoactivity [pro-S-(1-10)] in different somatostatin tissues as an index of tissue-specific N-terminal processing, 2) compared the concentrations of pro-S N- and C-terminal immunoreactive peptides, 3) used HPLC and region-specific RIAs directed against both the N- and C-terminal segments of pro-S to identify and characterize novel N-terminal peptides, 4) studied the tissue distribution and release of the N-terminal peptides; and 5) characterized and quantified a 7-kDa molecule equivalent to pro-S without the C-terminal S-28 sequence. Acetic acid (1 M)-pepstatin extracts of hypothalamus, cerebral cortex, antrum, jejunal mucosa, and pancreas were fractionated by reverse phase and gel permeation HPLCs. Whole tissue extracts as well as the column effluent were monitored by region-specific RIAs using antibodies against pro-S-(1-10), S-28-(1-12), and S-14. Other than the pancreas, all S-producing tissues were rich in pro-S-(1-10) LI. Its concentration was 1- to 4-fold lower than those of S-14 LI and S-28-(1-12) LI. Tissue pro-S-(1-10) LI was heterogeneous, consisting of at least eight molecular forms with respective mol wt of 1,000 (1 kDa), 1,500 (1.5 kDa), 2,500 (2.5 kDa), 3,500 (3.5 kDa), 4,500 (4.5 kDa), 7,000 (7 kDa), 8,000 (8 kDa), and 10,000 (10 kDa). Based on the simultaneous presence or absence of C-terminal immunoreactivity, the 10-kDa form corresponded to pro-S, 8 kDa to pro-S-(1-76), and 7 kDa to pro-S without the S-28 sequence. The predominant N-terminal forms corresponded to 1 kDa [pro-S-(1-10)] and 7 kDa. The 1-, 1.5-, 2.5-, and 7-kDa forms were identified as secretion products in portal blood or in medium from cultured 1027 B2 islet somatostatin cells.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Peptides derived by processing of rat prosomatostatin near the amino-terminus: characterization, tissue distribution, and release. 196 42

The effects of endogenous hypothalamic neurohormones and activators of second messenger signalling systems on the secretion of GH and on cell content of GH mRNA of cultured bovine adenohypophysial cells were studied. Synthetic bovine GH-releasing factor (bGRF; 100 nmol/l) increased secretion of GH by bovine adenohypophysial cells five-fold relative to control. Forskolin (an adenyl cyclase activator; 10 mumol/l) and the synthetic cyclic AMP analogue dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) increased secretion of GH by 1.9- and 1.7-fold respectively, relative to control. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA), provided at 1 mumol/l or 10 nmol/l, increased GH secretion by 6.6- and four-fold respectively, relative to control. Somatostatin-14 (SRIF-14) attenuated basal, bGRF-, forskolin- and dbcAMP-stimulated secretion of GH by 40, 49, 47 and 67% respectively, but did not, however, diminish PMA-stimulated GH secretion. The content of GH mRNA in cultured bovine adenohypophysial cells increased 2.2-, 1.7- and 3.2-fold by administration of bGRF, forskolin and PMA respectively, relative to control. Although GH mRNA content was unchanged by SRIF-14 treatment relative to control, SRIF-14 did reduce bGRF-stimulated bGH mRNA content by 67%. This study demonstrates that mechanisms subserving GH secretion in bovine adenohypophysial cells (e.g. adenyl cyclase and protein kinase C) may be coupled with mechanisms which regulate expression of the GH gene or with factors affecting message stability.
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PMID:Modulation of growth hormone (GH) secretion and GH mRNA levels by GH-releasing factor, somatostatin and secretagogues in cultured bovine adenohypophysial cells. 197 Oct 2

Receptor-dependent and -independent regulation of gastrin secretion from cultured human antral G cells was investigated. Human antral mucosal cell preparations that were enriched for G cells were obtained by sequential incubations with collagenase and ethylenediaminetetraacetic acid, centrifugal elutriation, and short-term culture. After a 2-day incubation period, gastrin- and somatostatin-containing cells accounted for 15% and 5%, respectively, of the total adhered-cell population. Forskolin, A23187, and beta-phorbol 12 myristate 13-acetate stimulated basal gastrin secretion from cultured human G cells in a concentration-dependent fashion. These results indicate that gastrin release could be mediated by elevations in cytosolic cyclic adenosine monophosphate levels, calcium influx, or activation of protein kinase C. A direct stimulatory role for bombesin- and gastrin-releasing peptide was supported by experiments showing concentration-dependent enhancement of gastrin release by bombesin from 0.01 fmol/L to 10 nmol/L. The putative bombesin antagonist [Leu13-psi-CH2NH-Leu14] bombesin augmented basal gastrin levels by itself and produced weak inhibition of bombesin-induced gastrin secretion from human antral G cells. Somatostatin potently suppressed forskolin- and bombesin-mediated gastrin release but did not significantly alter basal gastrin levels. These results suggest that bombesin and somatostatin directly activate and inhibit G-cell function via specific and sensitive receptors. Furthermore, the adenylate cyclase and phosphatidyl inositide second messenger systems seem to be intracellular mediators of gastrin secretion from human antral G cells.
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PMID:Gastrin secretion from human antral G cells in culture. 197 10

A primary culture of the canine jejunal submucosa has been established and used to investigate neuronal somatostatin release. Immunocytochemical characterization of the cultures demonstrated the presence of the following peptidergic neurons: neurotensin (30%), somatostatin (27%), vasoactive intestinal polypeptide (14%), neuropeptide Y (10%), and substance P (5%). No immunoreactive neurons were observed with the available antisera to galanin, gastrin-releasing peptide, and motilin. The concentration of somatostatin-like immunoreactivity, as determined by radioimmunoassay of cell extracts, was 358 +/- 105 pmol/well. Basal release of somatostatin was 4.4 +/- 0.9% total cell content and was significantly inhibited by the addition of substance P at 1 and 100 nM. The addition of the calcium ionophore, A23187, with phorbol 12-myristate 13-acetate stimulated somatostatin release in a concentration-dependent manner. These data indicate that short-term cultures of the jejunal submucosal plexus will be an excellent model for determination of the factors influencing the release of neural somatostatin.
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PMID:Canine jejunal submucosa cultures: characterization and release of neural somatostatin. 197 28

A primary culture of human antral somatostatin cells has been developed and used in release studies. The phorbol ester, phorbol 12 myristate 13-acetate, caused a concentration-dependent increase in immunoreactive somatostatin secretion with a 1-mumol/L concentration resulting in a 40-fold stimulation (basal 0.28% +/- 0.7% total cell content vs. 13.8% +/- 2.2% TCC, P less than 0.005). The calcium ionophore, A23187, resulted in a significant stimulation only at 1 mumol/L (basal 0.28% +/- 0.7% TCC vs. 2.2% +/- 0.5% total cell content, P less than 0.05). However, addition of the ionophore at 1 mumol/L with the phorbol ester resulted in a potentiation of the response at all concentrations tested. Removal of extracellular calcium by chelation with EGTA reduced the response to that seen with the phorbol ester alone. Forskolin at 0.1 mmol/L resulted in a five-fold increase (basal 0.6% +/- 0.2% total cell content vs. 2.8% +/- 0.9% total cell content, P less than 0.02) and was 1000-fold less potent than the phorbol ester. The peptides bombesin and gastrin at concentrations up to 1 mumol/L had no effect on basal secretion. Cholecystokinin-8 significantly stimulated somatostatin secretion with a maximal effect at 0.1 mumol/L resulting in an eightfold increase (basal 0.2% +/- 0.04% total cell content vs. 1.5% +/- 0.4% total cell content, P less than 0.02). These results indicate that human antral D cells are more responsive to agents acting through the c-kinase pathway (phorbol 12 myristate 13-acetate, A23187, and cholecystokinin) than adenylate cyclase (forskolin).
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PMID:Release of somatostatin immunoreactivity from human antral D cells in culture. 197 18

We undertook the present studies to explore the mechanisms by which carbachol inhibits the release of somatostatin-like immunoreactivity (SLI) from D cells. D cells were isolated from canine fundic mucosa by collagenase/EDTA dispersion followed by counterflow elutriation. Carbachol inhibited the release of SLI induced by forskolin, dibutyryl 3':5' cyclic adenosine monophosphate (cAMP), pentagastrin (PG), and 12-0-tetradecanoyl-phorbol-13-acetate in a fashion that could be prevented by pertussis toxin (PT) pretreatment of the D cells. Pertussis toxin also prevented the carbachol-induced inhibition of forskolin-stimulated cAMP generation and PG-stimulated [Ca2+]i mobilization. These data indicate that pertussis toxin sensitive inhibitory guanine nucleotide binding proteins mediate many of carbachol's inhibitory actions on D cells.
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PMID:Mechanisms for muscarinic inhibition of somatostatin release from canine fundic D cells. 197 5

Somatostatin and its longer-acting analog, octreotide acetate, can be used effectively for the treatment of nonendocrine gastrointestinal disorders. Octreotide has been shown to decrease pancreatic fistula output by suppressing exocrine pancreatic function. We believe that octreotide acetate may be useful to prophylaxis against the development of pancreatic fistulas following pancreatic resection and may reduce the enzymatic and volume output of established pancreatic fistulas. We also have shown that administration of octreotide acetate 2 hours before a high carbohydrate test meal reduces gut peptide levels, which increase following meal ingestion in patients with the dumping syndrome. Reduction of circulating peptides in these patients may slow gut motility and improve glucose regulation, thus, providing relief of postvagotomy dumping symptoms.
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PMID:Treatment of nonendocrine gastrointestinal disorders with octreotide acetate. 197 12

Prenatal administration of methylazoxymethanol acetate (MAM), which kills neuroblasts undergoing mitosis, was used to lesion striatal somatostatin neurons. Previous [3H]thymidine autoradiographic studies had indicated that striatal somatostatin neurons undergo their final mitotic division at Gestational Days (G) 15 and 16. Therefore, pregnant Sprague-Dawley rats received an intraperitoneal injection of MAM (25 mg/kg) on G15. Neurochemical and histological examination of the mature offspring indicated the loss of half the striatal aspiny interneurons in which somatostatin, neuropeptide Y, and NADPH diaphorase coexist, with relative sparing of the cholinergic interneurons and medium spiny projection cells. This prenatal MAM treatment was without apparent effect on the patch-matrix organization of the striatum.
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PMID:Loss of striatal somatostatin neurons following prenatal methylazoxymethanol. 197 8


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